Adolescent alcohol use is associated with myriad adverse legal, health, and educational consequences and contributes to the leading causes of mortality among youth. Yet despite the magnitude of this public health problem, treatment initiatives for youth remain inadequate. Given these data, the National Institute on Alcohol Abuse and Alcoholism identified the critical need for medications development research for youth (PA-10-100) with the goal of identifying promising agents for which large-scale clinical trials are justified. The long-term goal of this research program, now in its 20th year, is to improve pharmacotherapy for alcoholism. The major objective of this competing continuation (renewal) application is to address the urgent need for empirical data on medications that may benefit youth. For the past 10 years our research program has successfully paired human laboratory paradigms with ecological momentary assessment (EMA), whereby research participants use handheld electronic diaries to monitor their drinking, craving, and sensitivity to alcohol in real time in their natural environment Using this approach, we identified mechanisms by which medications act and patient characteristics that moderate these effects. The proposed study will test if and how topiramate (TPM), an anticonvulsant shown to be efficacious for treating adults, reduces drinking in youth To this end, we will randomize adolescents with AD (n = 160;ages 14-20) to TPM or placebo for 8 weeks, in combination with biweekly motivational enhancement therapy sessions, using a two-group, double-blind design. While at the target dose (200 mg/day) youth will complete EMA for 4 weeks in their natural environmentIn addition, youth will complete alcohol cue reactivity assessments in the laboratory to test the effects of TPM on cue-elicited craving and physiological reactivity in a controlled environmentYouth will complete 6- and 12-month follow-up assessments to determine whether any benefits are sustained. This study will provide much needed data on the tolerability and efficacy of TPM with adolescents, while adding important new information about the biobehavioral mechanisms of TPM action in youth. PUBLIC HEALTH RELEVANCE: This study will help to determine whether the medication, topiramate, reduces alcohol use among adolescents with alcohol dependence. It will also help answer the question, "How does topiramate reduce drinking in youth?" Understanding how topiramate may reduce drinking in adolescents would allow for a more targeted pharmacotherapeutic approach to treatment and help to identify additional medications that may hold promise for improving treatment outcomes for youth.